Transient Hypoxia Alters Striatal Catecholamine Metabolism in Immature Brain: An In Vivo Microdialysis Study

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Abstract
Microdialysis probes were inserted bilaterally into the striatum of 7-day-old rat pups (n = 30) to examine extracellular fluid levels of dopamine, its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). The dialysis samples were assayed by HPLC with electrochemical detection. Baseline levels, measured after a 2-h stabilization period, were as follows: dopamine, not detected; DOPAC, 617 .+-. 33 fmol/min; HVA, 974 .+-. 42 fmol/min; and 5-HIAA, 276 .+-. 15 fmol/min. After a 40-min baseline sampling period, 12 animals were exposed to 8% oxygen for 120 min. Hypoxia produced marked reductions in the striatal extracellular fluid levels of both dopamine metabolites (p < 0.001 by analysis of variance) and a more gradual and less prominent reduction in 5-HIAA levels (p < 0.02 by analysis of variance), compared with controls (n = 12) sampled in room air. In the first hour after hypoxia, DOPAC and HVA levels rose quickly, whereas 5-HIAA levels remained suppressed. The magnitude of depolarization-evoked release of dopamine (elicited by infusion of potassium or veratrine through the microdialysis probes for 20 min) was evaluated in control and hypoxic animals. Depolarization-evoked dopamine efflux was considerably higher in hypoxic pups than in controls; hypoxic (n = 7), 257 .+-. 32 fmol/min; control (n = 12), 75 .+-. 14 fmol/min (p < 0.001 by analysis of variance). These data demonstrate that a brief exposure to moderate hypoxia markedly disrupts striatal catecholamine metabolism in the immature rodent brain.